Candidate: Dr. Daniel A. Gray is a nephrologist who seeks an academic research career combining clinically relevant basic science work in renal transport physiology with patient care. He has a solid background in electrophysiology involving K+ channels in the rat collecting duct and now wants to extend this work to the mouse given the availability of important knock-out and transgenic animals. In particular, he seeks to gain skill at the microdissection required to isolate and record K+ currents from mouse collecting tubules. With more experience of this nature under his belt, Dr. Gray will be in a strong position to succeed as an independent investigator. Environment: Dr. Gray is fortunate to have Dr. Lawrence G. Palmer, a pioneer in the sudy of Na+ and K+ ion channels in the kidney, as his sponsor. Dr. Palmer continues to do experiments himself so that he is both accessible and able to pass on the "art" of ion channel recording. As a cosponsor, Dr. Lisa M. Satlin, pediatric nephrologist with an expertise in developmental expression of ion channles, brings not only experience relevant to AIM 3 of the reseach proposal but also a clinical perspective that nicely complements the role of Dr. Palmer. Research Proposal: "Basolateral principal cell K+ channels." The basolateral K+ conductance in principal cells plays a critical role in K+ and Na+ homeostasis but its underlying molecular determinants are unknown. This conductance has been electrophysiologically characterized (presented here in Preliminary Results) and the data strongly suggests that the K+ channel, Kir4.1, is responsible. This hypothesis will be confirmed with a combination of immunocytochemistry and patch-clamp studies in rat and an existing Kir4.1 knock-out mouse. Dietary and hormonal regulation as well as developmental expression of this channel will then be investigated to better understand the role of this important K+ pathway